Naloxone SR Capsules in Patients With Opioid Induced Constipation

Inclusion Criteria

• All subjects must give written informed consent
• Male or female subjects greater than 18 years of age
• Taking opioid full agonist therapy(oral or transdermal) for persistent non-cancer pain, for at least 4 weeks prior to baseline visit
• Subjects with at least a 3 week history of OIC prior to baseline; where bowel dysfunction is predominantly due to opioids and started following commencement of opioid therapy
• Subjects with <3 SBMs a week and experiencing one or more bowel symptoms (incomplete evacuation, straining, hard/small pellets) for 25% or more of bowel movements during the screening period
• Subjects must be willing to discontinue all current laxative (constipation) therapy. Bisacodyl will be provided and taken as required

Exclusion Criteria

• Women of childbearing potential, unless surgically sterile or using adequate contraception (either IUD, oral or depot contraceptive, or barrier plus spermicide). Women using oral contraception must have started using it at least 2 months prior to enrolment
• Women who are pregnant or breastfeeding
• Symptoms suggestive of non-opioid related bowel dysfunction (e.g. IBS - intermittent constipation or diarrhoea) or have diarrhoea or loose stools in the 4 weeks prior to baseline
• History of chronic constipation prior to commencing opioid therapy
• Gastrointestinal disorders known to affect bowel transit, or contribute to bowel dysfunction (other than OIC)
• Chronic faecal incontinence
• Subjects who have a colostomy, ileostomy, or colectomy with ileorectal anastomosis
• Subjects with a history of neoplastic disease within 5 years (except for basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin)
• Subjects taking opioids for the management of drug addiction Subjects who do not meet any of the following criteria regarding baseline medications. Analgesia (including opioids and NSAIDs) should be stable throughout the trial.
• Any baseline analgesia must have been administered at a stable dose for a minimum of 4 weeks. If non-opioid analgesia recently discontinued, must have stopped at least 4 weeks prior to baseline
• Laxatives (outside that allowed by the protocol) are not permitted; these agents must have been discontinued at the screening visit.
• Use of drugs known to affect gut transit time (other than opioids) are not permitted (see Section 6.9 for exceptions)
• Use of mixed agonist/antagonist, or partial agonist opioids are not permitted (e.g. buprenorphine, pentazocine, cyclazocine, nalbuphine, nalorphine)
• Experimental agents must have been discontinued at least 8 weeks prior to screening, or for a period equivalent to 5 half-lives (t½) of the agent (whichever is longer)
• Subjects with a history of clinically significant and/or persistent disorder that, in the investigators opinion, may affect the clinical trial assessments
• Subjects with any laboratory tests considered clinically significant at screening.
• Subjects not ambulatory i.e. bedridden or require use of a commode
• Subjects who will be unavailable for the duration of the trial, likely to be non-compliant with the protocol, or who are felt to be unsuitable by the Investigator for any other reason